Cancer is one of the major causes of deaths in the world. The number of new cancer cases is reported to be more than 10 million people every year and is estimated to be 15 million people by 2020. Cancer-related deaths are 6 million every year, representing 12% of deaths worldwide (National Cancer Control Programmes: Policies and Managerial Guidelines, World Health Organization Geneva, 2002). In the United States, the number of new cancer cases and deaths in 2005 is estimated to be 1,372,910 and 570,280 people, respectively (Cancer Facts & Figures-2005, American Cancer Society (ACS), Atlanta, Ga., 2005). In recent years, much progress has been made toward understanding the molecular and cellular biology of cancers. Many important contributions have been made by the identification of several key genetic factors associated with cancers. However, there are still some limitations in the use of biological markers for detecting cancers, suggesting that identification of new markers for diagnosing cancers is needed.
One of the contributing factors for cancers is the genes associated with cell cycle control. Thus, future strategies for the prevention and treatment of prostate cancer will be focused on identification, isolation and elucidation of genes involved in cell cycle regulation. A human kinase interacting protein 2 (KIP2) gene, candidate tumor suppressor gene (Matsuoka et al. (1995) Genes Dev 9:650-62), is a member of Cip/Kip family involved in the negative regulation of the cell cycle at the G1 checkpoint (Lee et al. (1995) Genes Dev 9:639-49; Harper and Elledge, (1996) Curr Opin Genet Dev 6:56-64; Sherr, (1996) Science 274:1672-7; Lee and Yang, (2001) Cell Mol Life Sci 58:1907-22). The tumor suppressor activity of KIP2 was shown to be mediated via its interaction with cyclin A-CDK2 (Adkins and Lumb, (2002) Proteins 46:1-7) or proliferating cell nuclear antigen (PCNA; Watanabe et al. (1998) Proc Natl Acad Sci USA 95:1392-1397). Overexpression of KIP2 was reported to arrest cells in G1 (Lee et al. (1995) Genes Dev 9:639-49; Matsuoka et al. (1995) Genes Dev 9:650-62). Decreased expression of KIP2 has been observed in many cancers (Chung et al. (1996) Hum Mol Genet 5:1101-8; Oya and Schulz, (2000) Br J Cancer 83:626-31; Dauphinot et al. (2001) Oncogene 20:3258-65; Ito et al. (2001) Oncology 61:221-5). These findings strongly implicate that KIP2 may have a role in the tumorigenic process of cancers. Therefore, the discovery of gene variants of KIP2 from cancers may be important targets for diagnostic markers of cancers.